The career development plan described in this competing renewal application will allow the applicant to continue the development and expansion of his research career into new areas of investigation that complement current areas of expertise. The applicant has extensive training and experience in behavioral neuropharmacology and substance abuse with primary expertise in the neuropharmacology of CMS stimulants. During the previous funding period, the applicant developed in vivo microdialysis techniques in conscious monkeys trained to self-administer cocaine and related stimulants in order to determine neurochemical changes associated with the behavioral and reinforcing properties of abused stimulants. In addition, the development of positron emission tomography (PET) imaging techniques in conscious monkeys expanded further the applicant's ability to characterize and quantify the CMS effects of abused stimulants. More recent efforts have focused on the development of functional magnetic resonance imaging (fMRI) in conscious monkeys to document with high temporal and spatial resolution drug-induced changes in CMS activity. A major focus of the research plan will involve the pharmacological manipulation of monoamine and glutamate systems to assess potential changes in sensitivity to the CNS effects of cocaine. The studies proposed will provide an innovative preclinical model to identify useful pharmacotherapies for stimulant abuse. In addition to research activities, the applicant will commit effort to educational activities related to biomedical research and substance abuse. The host institution, Emory University, has a well-established program related to neuroscience and substance abuse research that is ideally suited to the career development plan. The University will provide the necessary resources and adequate time to ensure the development of the applicant as a productive, independent research scientist. The long-term commitment and support provided by continuation of the Independent Scientist Award will provide the opportunity to develop and integrate new skills and expertise into a unique multidisciplinary research program in substance abuse.